Functional antagonism between STAT3 and SMAD4 regulates EMT

Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. We identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition in mutant KRAS tumors. RNA sequencing was performed with murine cells expressing mutant KRAS either overexpressing hyperactive STAT3Y640, or CRISPR-mediated knockout of STAT3, SMAD4, or KRAS. Excel files of differential expression compared to control mutant RAS cells or fpkm files are provided., Total RNA was isolated using the PureLink RNA kit (ThermoFisher) and phenol-extracted. Whole exome RNA sequencing with bioinformatics was performed by Novogene Corp.. Excel data files include: 1) KRASG12D:p53null mouse embryo fibroblasts (MEF KP)(Ischenko et al. 2013 PNAS) and MEF KP expressing hyperactive STAT3 Y640F, 2) Murine KRASG12D:p53R172H PDAC (KPC)(Hingorani et al. 2005 Cancer Cell) and KPC KRAS knockout cells, 3) KPC and KPC STAT3 knockout cells, 4) KPC SMAD4 knockout cells., , # Functional antagonism between STAT3 and SMAD4 regulates EMT ### Contributors: Stephen DAmico, Varvara Kirillov, Oleski Petrenko, and Nancy Reich **Description**: We evaluated STAT3 as a cancer dependency in KRAS-mediated tumorigenesis with established models using mouse embryonic fibroblasts and pancreatic ductal adenocarcinoma cells. The data highlight antagonistic epistasis between SMAD4 and STAT3, where SMAD4 expressing tumors are poorly differentiated in the absence of STAT3, while SMAD4 deficient tumors are well-differentiated in the presence of STAT3. **Techniques**: Data include RNA Sequencing analysis of genetically modified tumorigenic cells lines. Total RNA was isolated using the PureLink RNA kit (ThermoFisher) and phenol-extracted. Whole exome RNA sequencing with bioinformatics was performed by Novogene Corp.. Excel data files are included: 1\) Gene ID, log fold change, and fpkm for RNA expression in KRASG12D:p53null mouse embryo fibroblasts (MEF KP)(Ischenko et al. 20...KRAS致癌突变是癌症中最为常见的突变类型之一。经典肿瘤模型指出，上皮特征的丧失以及间充质表型的获得，与癌症侵袭性及治疗耐药性密切相关。本研究将STAT3(信号转导与转录激活因子3, Signal Transducer and Activator of Transcription 3)鉴定为突变KRAS肿瘤中转化生长因子-β(TGF-β, Transforming Growth Factor-β)诱导的上皮-间质转化(EMT, Epithelial-Mesenchymal Transition)的遗传修饰因子。我们对表达突变KRAS的小鼠细胞分别开展了高活性STAT3Y640过表达，或通过CRISPR介导的STAT3、SMAD4或KRAS基因敲除，并进行了RNA测序。本数据集提供了相较于对照突变RAS细胞的差异表达Excel文件，以及每百万片段转录本数(fpkm, Fragments Per Kilobase of transcript per Million mapped reads)文件。 总RNA提取采用PureLink RNA试剂盒(赛默飞世尔科技，ThermoFisher)，并经酚类试剂抽提。全外显子组RNA测序及生物信息学分析由诺禾致源公司(Novogene Corp.)完成。 Excel数据文件包括： 1. 携带KRASG12D突变且p53缺失的小鼠胚胎成纤维细胞(MEF KP，Ischenko等，2013年《美国国家科学院院刊》)以及表达高活性STAT3 Y640F的MEF KP细胞； 2. 携带KRASG12D;p53 R172H突变的小鼠胰腺导管腺癌(PDAC, Pancreatic Ductal Adenocarcinoma)细胞(KPC，Hingorani等，2005年《癌细胞》)以及KPC KRAS基因敲除细胞； 3. KPC细胞以及KPC STAT3基因敲除细胞； 4. KPC SMAD4基因敲除细胞。 # STAT3与SMAD4的功能拮抗调控上皮-间质转化 贡献者：Stephen DAmico、Varvara Kirillov、Oleski Petrenko及Nancy Reich **描述**：我们利用小鼠胚胎成纤维细胞与胰腺导管腺癌细胞的已建模型，评估了STAT3作为KRAS介导的肿瘤发生过程中癌症依赖因子的作用。本数据揭示了SMAD4与STAT3之间的拮抗上位效应：在STAT3缺失时，表达SMAD4的肿瘤呈低分化状态；而在STAT3存在时，SMAD4缺陷的肿瘤呈高分化状态。 **技术方法**：本数据集包含对基因修饰致瘤细胞系的RNA测序分析。总RNA采用PureLink RNA试剂盒(赛默飞世尔科技，ThermoFisher)提取并经酚类试剂抽提。全外显子组RNA测序及生物信息学分析由诺禾致源公司(Novogene Corp.)完成。 Excel数据文件包含： 1) 携带KRASG12D:p53null突变的小鼠胚胎成纤维细胞(MEF KP，Ischenko等，20...)的RNA表达相关数据，包括基因ID、对数倍数变化值及fpkm值。